What is the appropriate management for a patient with leukocytosis, erythrocytosis, hyperhemoglobinemia, and hyperhematocritemia, along with vitamin D deficiency and hyperferritinemia?

Management of Leukocytosis, Erythrocytosis, and Hyperferritinemia

This patient requires immediate evaluation for polycythemia vera with JAK2 mutation testing and serum erythropoietin level, while simultaneously addressing the vitamin D deficiency and investigating the cause of hyperferritinemia, which is most likely related to inflammation or chronic disease rather than hemophagocytic lymphohistiocytosis. 1

Immediate Diagnostic Workup

Erythrocytosis Evaluation

• Order JAK2 mutation testing and serum erythropoietin level as the first-line diagnostic tests to distinguish polycythemia vera from secondary erythrocytosis 1
• Review peripheral blood smear to assess red cell morphology and rule out microcytosis from iron deficiency 1
• If JAK2 mutation is positive with low EPO, the diagnosis is polycythemia vera and requires bone marrow biopsy showing panmyelosis 1
• If JAK2 mutation is negative with low EPO, consider bone marrow biopsy to evaluate for clonal abnormalities and test for other myeloproliferative neoplasm markers 1

Critical Iron Status Assessment

• The elevated ferritin (689 ng/mL) with normal iron saturation (21%) suggests inflammation or chronic disease, NOT iron overload 2
• Despite the elevated ferritin, assess for functional iron deficiency by evaluating transferrin saturation and reviewing the peripheral smear for microcytic hypochromic cells 1
• Iron deficiency in erythrocytosis is dangerous and increases stroke risk, so this must be definitively ruled out 1, 3
• In a patient with erythrocytosis, ferritin can be misleadingly elevated due to inflammation while true iron deficiency exists 3

Leukocytosis Significance

• The presence of leukocytosis (WBC 11.0) with thrombocytosis (platelets 336, upper normal) strongly suggests polycythemia vera and increases the likelihood of JAK2 mutation positivity 1
• The neutrophilia (absolute neutrophils 7.8) supports a myeloproliferative process rather than reactive leukocytosis 1

Hyperferritinemia Investigation

Differential Diagnosis Priority

• Ferritin of 689 ng/mL is elevated but NOT extreme hyperferritinemia (which is defined as >10,000 ng/mL) 2, 4
• At this level, the most common causes are: chronic inflammation, liver disease, or hematologic malignancy (such as polycythemia vera) 2
• Hemophagocytic lymphohistiocytosis is extremely unlikely with ferritin <10,000 ng/mL and absence of fever, splenomegaly, or other HLH criteria 2, 5, 4
• In adults with ferritin >10,000 µg/L, HLH accounts for only 14.2% of cases, making it even less likely at this ferritin level 4

Additional Workup Needed

• Check liver function tests (AST, ALT, bilirubin) to evaluate for liver disease as a cause of hyperferritinemia 2
• Review for signs of chronic inflammation or infection that could explain the elevated ferritin 2
• The hyperferritinemia will likely resolve if the underlying myeloproliferative disorder is treated 2

Vitamin D Deficiency Management

• With vitamin D level of 29 ng/mL (below 30 ng/mL threshold), initiate vitamin D2 50,000 units orally every month for 6 months 6
• This recommendation applies specifically to patients with chronic kidney disease (GFR <30 mL/min/1.73 m²), but the same threshold is used in general practice 6
• Recheck 25(OH) vitamin D level after 6 months of supplementation 6

Monitoring and Follow-up

Hematologic Monitoring

• If polycythemia vera is confirmed, monitor for hyperviscosity symptoms (headache, increasing fatigue) with hemoglobin >20 g/dL and hematocrit >65% 6, 1
• The current hemoglobin of 16.1 g/dL and hematocrit of 48.5% do NOT meet criteria for therapeutic phlebotomy 6
• Repeated routine phlebotomies are contraindicated due to risk of iron depletion, decreased oxygen-carrying capacity, and stroke 6

Ongoing Laboratory Surveillance

• Recheck CBC with differential in 3 months to monitor for progression of erythrocytosis or leukocytosis 6
• Monitor ferritin levels after initiating treatment for any identified myeloproliferative disorder 2
• Reassess vitamin D level after 6 months of supplementation 6

Critical Pitfalls to Avoid

• Do not assume elevated ferritin indicates iron overload or hemophagocytic lymphohistiocytosis without additional supporting evidence 2, 4
• Do not perform therapeutic phlebotomy based solely on elevated hemoglobin/hematocrit without documented hyperviscosity symptoms and values >20 g/dL/>65% 6
• Do not overlook iron deficiency in the setting of erythrocytosis, as ferritin can be falsely elevated by inflammation while true iron deficiency exists 3
• Do not delay JAK2 testing, as this is the single most important diagnostic test to guide management 1